ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.2153A>C (p.His718Pro)

dbSNP: rs587778983
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT) RCV000075557 SCV000106554 likely pathogenic Lynch syndrome 2019-06-21 reviewed by expert panel curation Multifactorial likelihood analysis poster probability between 0.95-0.99
Labcorp Genetics (formerly Invitae), Labcorp RCV000694232 SCV000822667 likely pathogenic Hereditary nonpolyposis colorectal neoplasms 2022-08-16 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MLH1 protein function. ClinVar contains an entry for this variant (Variation ID: 90071). This missense change has been observed in individual(s) with colorectal adenomas (PMID: 19324997, 21520333). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 718 of the MLH1 protein (p.His718Pro).
Mendelics RCV002247469 SCV002517621 pathogenic Muir-Torré syndrome 2022-05-04 criteria provided, single submitter clinical testing

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