ClinVar Miner

Submissions for variant NM_005957.5(MTHFR):c.584C>T (p.Ala195Val)

dbSNP: rs760161369
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences RCV001353257 SCV001548193 likely pathogenic Homocystinuria due to methylene tetrahydrofolate reductase deficiency criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV001353257 SCV003522799 likely pathogenic Homocystinuria due to methylene tetrahydrofolate reductase deficiency 2023-09-19 criteria provided, single submitter clinical testing This variant is present in population databases (rs760161369, gnomAD 0.02%). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies have shown that this missense change affects MTHFR function (PMID: 27743313). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1048667). This missense change has been observed in individual(s) with severe methylenetetrahydrofolate reductase deficiency (PMID: 21131308, 25736335). It has also been observed to segregate with disease in related individuals. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 195 of the MTHFR protein (p.Ala195Val).
Baylor Genetics RCV004570861 SCV005056005 likely pathogenic Neural tube defects, folate-sensitive 2023-12-07 criteria provided, single submitter clinical testing

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