Submissions for variant NM_000372.5(TYR):c.938_939dup (p.Ser314fs)

dbSNP: rs867751958

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001009246	SCV001169067	likely pathogenic	not provided	2019-02-06	criteria provided, single submitter	clinical testing	The c.938_939dupCC variant in the TYR gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.938_939dupCC variant causes a frameshift starting with codon Serine 314, changes this amino acid to a Proline residue, and creates a premature Stop codon at position 6 of the new reading frame, denoted p.Ser314ProfsX6. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.938_939dupCC variant is observed in 1/16252 alleles from individuals of African background in large population cohorts (Lek et al., 2016). We interpret c.938_939dupCC as a likely pathogenic variant.
Invitae	RCV001009246	SCV004482842	pathogenic	not provided	2023-02-21	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser314Profs*6) in the TYR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TYR are known to be pathogenic (PMID: 23504663). This variant is present in population databases (no rsID available, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with TYR-related conditions. ClinVar contains an entry for this variant (Variation ID: 818005). For these reasons, this variant has been classified as Pathogenic.